Evidence map›Paper›PMID 22549432›Full record

Trial reportArthritis and rheumatism2012

N-acetylcysteine reduces disease activity by blocking mammalian target of rapamycin in T cells from systemic lupus erythematosus patients: a randomized, double-blind, placebo-controlled trial.

Zhi-Wei Lai, Robert Hanczko, Eduardo Bonilla, Tiffany N Caza, Brandon Clair, Adam Bartos, Gabriella Miklossy, John Jimah, Edward Doherty, Hajra Tily and 9 more

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Arthritis and rheumatism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 235 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
235citing papers in PubMed, 4 pooled it
12.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

235 citing papers in PubMed, 4 syntheses or guidelines pooled it, 401 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
  6. Trial
  7. Trial
  8. Trial
  9. Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. Article
  19. Review
  20. Review

175 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 1 institution in 1 country.

Zhi-Wei LaiState University of New York, Upstate Medical University, College of Medicine, Syracuse, New York 13210, USA.
Robert Hanczko
Eduardo Bonilla
Tiffany N Caza
Brandon Clair
Adam Bartos
Gabriella Miklossy
John Jimah
Edward Doherty
Hajra Tily
Lisa Francis
Ricardo Garcia
Maha Dawood
Jianghong Yu
Irene Ramos
Ioana Coman
Stephen V Faraone
Paul E Phillips
Andras Perl
SUNY Upstate Medical University · US

Funding

SLE Treatment with N-acetylcysteineU01AR076092 · NIAMS · UPSTATE MEDICAL UNIVERSITY · PI Michael P McDermott, Andras Perl · 2020 to 2026
$7.9M
Metabolic Control of T-cell Lineage Specification in SLER01AI072648 · NIAID · UPSTATE MEDICAL UNIVERSITY · PI PERL, ANDRAS · 2008 to 2024
$6.1M
Treatment of SLE with N-acetylcysteineR01AT004332 · NCCIH · UPSTATE MEDICAL UNIVERSITY · PI PERL, ANDRAS · 2008 to 2011
$1.6M
NCCIH NIH HHS AT-004332NCCIH NIH HHS R01 AT004332NIAID NIH HHS AI-072648NIAID NIH HHS R01 AI072648NIAMS NIH HHS U01 AR076092
6 · The paper itself

Abstract

objectiveSystemic lupus erythematosus (SLE) patients exhibit T cell dysfunction, which can be regulated through mitochondrial transmembrane potential (Δψm) and mammalian target of rapamycin (mTOR) by glutathione (GSH). This randomized, double-blind, placebo-controlled study was undertaken to examine the safety, tolerance, and efficacy of the GSH precursor N-acetylcysteine (NAC).

methodsA total of 36 SLE patients received either daily placebo or 1.2 gm, 2.4 gm, or 4.8 gm of NAC. Disease activity was evaluated monthly by the British Isles Lupus Assessment Group (BILAG) index, the SLE Disease Activity Index (SLEDAI), and the Fatigue Assessment Scale (FAS) before, during, and after a 3-month treatment period. Mitochondrial transmembrane potential and mTOR were assessed by flow cytometry. Forty-two healthy subjects matched to patients for age, sex, and ethnicity were studied as controls.

resultsNAC up to 2.4 gm/day was tolerated by all patients, while 33% of those receiving 4.8 gm/day had reversible nausea. Placebo or NAC 1.2 gm/day did not influence disease activity. Considered together, 2.4 gm and 4.8 gm NAC reduced the SLEDAI score after 1 month (P = 0.0007), 2 months (P = 0.0009), 3 months (P = 0.0030), and 4 months (P = 0.0046); the BILAG score after 1 month (P = 0.029) and 3 months (P = 0.009); and the FAS score after 2 months (P = 0.0006) and 3 months (P = 0.005). NAC increased Δψm (P = 0.0001) in all T cells, profoundly reduced mTOR activity (P = 0.0009), enhanced apoptosis (P = 0.0004), reversed expansion of CD4-CD8- T cells (mean ± SEM 1.35 ± 0.12-fold change; P = 0.008), stimulated FoxP3 expression in CD4+CD25+ T cells (P = 0.045), and reduced anti-DNA production (P = 0.049).

conclusionThis pilot study suggests that NAC safely improves lupus disease activity by blocking mTOR in T lymphocytes.

Indexed as

AcetylcysteineAdultDouble-Blind MethodFemaleFree Radical ScavengersHumansLupus Erythematosus, SystemicMaleMembrane Potential, MitochondrialMiddle AgedPilot ProjectsPlacebosSeverity of Illness IndexT-LymphocytesTOR Serine-Threonine KinasesTreatment OutcomeAcetylcysteineFree Radical ScavengersPlacebosTOR Serine-Threonine Kinases

Identifiers

PMID22549432
PMCPMC3411859
OpenAlexW2015010210

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.